title: Pyrethroid mode(s) of action in the context of Food Quality Protection Act (FQPA) regulation.
abstract: A Scientific Advisory Panel (SAP) in June 2009 concluded that a common mode of action existed for pyrethroids, with two subgroups. The purpose of this SAP was to advise the U.S. Environmental Protection Agency on the validity of regulation of pyrethroids as a single class under the Food Quality Protection Act of 1996. Two types of pyrethroid action were first described for clinical signs in the rat and clinical signs/nerve effects in the cockroach. In insects, Type I clinical signs correlate with repetitive firing in nerve axons, especially fine sensory axons. The Na(+) inward current is via a TTX-sensitive voltage-gated sodium channel (VGSC). Type II (α-CN) effects on VGSCs do not include repetitive firing following stimulation in these axons. Instead, Type II effects on VGSCs include prolonged Na(+) tail currents along with depolarization of nerve membrane. Other Type II effects have been measured on VG Ca(2+) and K(+) channels and VG and GABA-activated Cl(-) channels. In conclusion, in vivo pyrethroid effects in mammals should be linked with specific channel effects, allowing the use of specific clinical signs or ion channel effects for pyrethroid risk assessment.
authors.affiliation: FMC Corporation, Ewing, New Jersey 08628, United States.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Gammon
authors.forename: Michael F
authors.initials: MF
authors.lastname: Leggett
authors.forename: John M
authors.initials: JM
authors.lastname: Clark
mesh_terms: D000818:Animals; D003058:Cockroaches; D005506:Food Contamination / Q000331:legislation & jurisprudence* / Q000517:prevention & control; D007306:Insecticides; D007473:Ion Channels / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects; D011041:Poisoning; D011722:Pyrethrins / Q000506:poisoning*; D051381:Rats; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D007306:Insecticides; D007473:Ion Channels; D011722:Pyrethrins